A method of providing an ion packet to an analyzer section of a mass spectrometer from an ion beam, a pulser which can execute such a method, and a mass spectrometer which includes such a pulser. In the method, a field pulse is applied to extract an ion packet from the beam at a sideways direction to the beam and provide it to a mass analyzer section of the mass spectrometer, which pulse simultaneously causes non-extracted ions of the beam to be deflected onto an electrode of opposite charge. The pulse ON time is significantly longer than conventionally used. For example, the pulse ON time may be longer than the pulse OFF time or at least twice as long as or several times longer than required to extract the ion packet and provide it to the mass analyzer section, so as to reduce stray ions entering the mass analyzer section. Preferably, the pulse ON time is the time required for ions of a predetermined highest mass of interest to be analyzed by the analyzer section, minus the time required to refill the region of the beam from which the ion packet is extracted with ions of the predetermined highest mass. ion leakage into the mass spectrometer section between packet extractions, and hence detected noise, can be reduced.
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18. A mass spectrometer comprising: (a) an analyzer section; and (b) a pulser having: a set of electrodes which can maintain an ion beam and to which a potential difference pulse can be applied to extract an ion packet from the beam at a sideways direction to the beam and provide said ion packet to the mass analyzer section, which pulse simultaneously causes non-extracted ions of the beam to be deflected onto an electrode of opposite charge; and (c) a power supply to provide a series of pulses as a pulse train to the electrode set, in which a pulse ON time of each cycle is longer than the pulse OFF time, so as to reduce stray ions entering the mass analyzer section.
1. A method of providing an ion packet to an analyzer section of a mass spectrometer from an ion beam, comprising: applying a field pulse to extract an ion packet from a region of the beam at a sideways direction to the beam and provide said ion packet to a mass analyzer section of the mass spectrometer, which pulse simultaneously causes non-extracted ions of the beam to be deflected onto an electrode of opposite charge to said non-extracted ions; wherein a pulse ON time is at least twice as long as a pulse ON time required to extract the ion packet and provide said ion packet to the mass analyzer section, so as to reduce stray ions entering the mass analyzer section.
12. A pulser to provide an ion packet to an analyzer section of a mass spectrometer from an ion beam, comprising: (a) a set of electrodes which can maintain an ion beam and to which a potential difference pulse can be applied to extract an ion packet from the beam at a sideways direction to the beam and provide said ion packet to a mass analyzer section of the mass spectrometer, which pulse simultaneously causes non-extracted ions of the beam to be deflected onto an electrode of opposite charge; and (b) a power supply to provide a series of pulses as a pulse train to the electrode set, in which a pulse ON time of each cycle is longer than the pulse OFF time, so as to reduce stray ions entering the mass analyzer section.
5. A method of providing an ion packet to an analyzer section of a mass spectrometer from an ion beam, comprising: (a) passing an ion beam between first and second electrodes and across an opening in the second electrode; and (b) applying a potential difference pulse across the electrodes such that during a pulse ON time, ions of a region of the beam adjacent the opening just before the pulse is applied are extracted through the opening as an ion packet and provided to a mass analyzer section of the mass spectrometer while other ions of the beam are caused to be deflected onto the second electrode which is oppositely charged from the ions; wherein the pulse ON time is at least twice as long as a pulse ON time required to extract the ion packet so as to reduce stray ions entering the mass analyzer section.
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This invention relates mass spectrometry and an in particular to a method of generating ion pulses (sometimes referred to as ion "packets") from an ion beam.
Time-of-flight mass spectrometers (TOFMS) are widely used to identify molecular structures in chemistry, bioscience, drug discovery and the like. The advantages of using TOFMS include its unlimited mass range, precise mass determination and the ability to detect transient signals.
For TOFMS analysis, ions are detected in the form of short bunches (or "packets") of several nanoseconds in duration. These short ion bunches are produced by either pulsed ion generation methods such as pulsed laser desorption/ionization (LDI) or by extracting them from an ion beam which is continuously generated. Electrospray (ES) and chemical ionization (CI) for instance, are continuous ionization techniques widely used for drug and biomolecule analysis. Continuous ionization by inductively coupled plasma (ICP) is an advanced technique for elemental analysis.
To produce ion packets from a continuous ion beam, a device as shown in
1. Ion filling period: A continuous ion beam 14 generated by an ion source 10 (which may be ES, CI, ICP or any other ion source generating a continuous beam) is directed into the region between a repeller electrode R and across grid 24 of electrode P0 (which is parallel to electrode R) and is collected at a collector electrode (basically the same as electrode 146 shown in FIG. 4). The travel direction of ions is parallel to the electrodes. During this period, the voltages applied to repeller R and electrode P0 are nearly the same, as indicated by pulse OFF regions 43 of a typical waveform 40 applied between R and P0 (see FIG. 2A). This results in a time 46 during which ions can fill the region over grid 24 and continue to pass thereover for collection by a collection electrode beyond R and P0 The filling time depends on the ion energy and mass of the ions to be analyzed and is generally of several hundred nanoseconds to several microseconds. By "filling time" in this context is referenced the time it takes to establish the beam containing the ions of highest predetermined mass of interest across grid 24.
2. When the region across grid 24 is filled with ions of interest, an electrical pulse (extraction pulse) 42 is applied to repeller R to form an accelerating field between R and P0. Ions are bundled into a packet 28 and accelerated in the perpendicular direction of the original travel for provision to a mass analyzer section of a mass spectrometer. The duration 44 of the extraction pulse is determined by the time required to accelerate ions of all mass out of the ion pulser, i.e. to pass grid 24 and is generally 1 to 3 microseconds in a conventional TOFMS.
Steps 1 and 2 above are repeated during the entire sample analysis, and the repetition rate is dependent of the time for ions of maximum molecular weight of interest to reach a detector 180 of the mass analyzer. The flight time for the ions in the mass analyzer is a function of mass to charge ratio of ions and many other mechanical and electrical parameters as well. For a typical mass analyzer in ICP detection, the maximum flight time is about 40 μs.
In a conventional TOFMS, the extraction pulse is turned off after 1 to 3 μs and ions begin to refill the ion pulser. Up to the time the next extraction pulse is applied, there is a period that ions can "leak" from the ion pulser and be accelerated toward the detector. The leakage is a result of ion diffusion and space charge repulsion. Leakage ions 32 generate a continuous background noise in an acquired mass spectrum and limit signal-to-noise ratio, and hence the sensitivity of detection. That is, referring to
U.S. Pat. No. 5,654,543 describes a method to reduced the above unwanted background noise by utilized an energy discrimination device. Using this method, unwanted species can be effectively blocked if they remain electrically charged. However, in many applications, large amounts of ions are sampled. These ions can become neutralized due to collisions with residual species in the vacuum chamber. Such neutral species retain the velocity of the ions and can reach the detector without being blocked by the energy discriminator. The resulting background noise originated from such neutral species has been experimentally observed (see P. Mahoney et al., J Am Soc Mass Spectrom, 8, 166-124 (1997).
It would be desirable then if a means could be found of reducing background noise resulting from the above described leakage ions. It would further be desirable if such a means was relatively simple to construct and use.
The present invention then, provides a method for reducing the above described background noise. In one aspect, the method provides an ion packet to an analyzer section of a mass spectrometer from an ion beam. A field pulse is applied to extract an ion packet from the beam at a sideways direction to the beam and provide it to a mass analyzer section of the mass spectrometer. This pulse simultaneously causes non-extracted ions of the beam to be deflected onto an electrode of opposite charge. A pulse ON time is at least twice as long (and optionally even three or four times as long) as required to extract the ion packet and provide it to the mass analyzer section, so as to reduce stray ions entering the mass analyzer section. In one aspect, a series of such pulses are applied as a pulse train such that during pulse ON times ion packets are extracted while other ions of the beam are deflected onto the second electrode.
In one aspect of the method, an ion beam is passed between first and second electrodes and across an opening in the second electrode. A potential difference pulse is applied across the electrodes such that during a pulse ON time, ions of the beam adjacent the opening just before the pulse is applied are extracted through the opening as an ion packet and provided to a mass analyzer section of the mass spectrometer, while other ions of the beam are caused to be deflected onto the second electrode which is oppositely charged from the ions. The pulse ON time may, for example, be at least twice as long as required to extract the ion packet so as to reduce stray ions entering the mass analyzer section. A series of such pulses may be applied as a pulse train such that during pulse OFF times the ion beam passes across the opening, and during pulse ON times ion packets are extracted while other ions of the beam are deflected onto the second electrode.
While various values of pulse ON time may be applied, the pulse ON time may be longer than the pulse OFF time. For example, pulse ON time may be at least twice as long (or four, or even ten times). In one embodiment, the pulse ON time is the time required for ions of a predetermined highest mass of interest to be analyzed by the analyzer section, minus the time required to refill the region of the beam from which the ion packet is extracted with ions of the predetermined highest mass (in some embodiments, the region across the opening). By "filling" or "refilling" the region in this context, is referenced that those ions of the predetermined mass have been re-established across the region from which the packets are extracted (in some embodiments, the region across the opening). The relative pulse ON and OFF times are optionally adjusted for the particular mass spectrometer to minimize background.
The present invention further provides a pulser in which one or more methods of the present invention can be executed, so as to provide an ion packet to an analyzer section of a mass spectrometer from an ion beam. The pulser includes a set of electrodes which can maintain an ion beam and to which a potential difference pulse can be applied to extract an ion packet from the beam at a sideways direction to the beam and provide it to a mass analyzer section of the mass spectrometer. The pulse simultaneously causes non-extracted ions of the beam to be deflected onto an electrode of opposite charge. A power supply provides the series of pulses as a pulse train to the electrode set, as described in the method above, so as to reduce stray ions entering the mass analyzer section.
In one aspect, the electrode set includes the first and second electrodes described above. Such electrodes may face one another with a gap between them which is narrower adjacent one side of the opening than at an opposite side of the opening, such that the ion beam can initially pass across the opening from the narrower side to the opposite side. In one configuration the first and second electrodes may be two parallel members with opposed inwardly directed extensions to define the narrower gap on the one side. The present invention further provides a mass spectrometer which includes the pulser and mass analyzer, of a configuration already described.
The various aspects of the present invention can provide any one or more of the following and/or other useful benefits. For example, by using an extraction pulse as described, the leakage of ions into the mass analyzer can be inhibited. As a result, noise at the detector can be reduced. Furthermore, the pulser may be of relatively simple construction.
Embodiments of the invention will now be described with reference to the drawings, in which:
FIGS. 2(A) and 2(B) illustrate the voltage waveforms applied to a pulser of the construction of
To facilitate understanding, identical reference numerals have been used, where practical, to designate identical elements that are common to the figures
In the present application, unless a contrary intention appears, the following terms refer to the indicated characteristics. Words such as "forward" are used in a relative sense only, generally with forward referring to a direction of ion flow. A "set" may have any number of multiple members (for example, two or more electrodes). Reference to a singular item, includes the possibility that there are plural of the same items present. Potentials are relative. All patents and other cited references are incorporated into this application by reference.
Referring to
The pulser 18 may be part of a conventional mass spectrometer such as a TOFMS illustrated schematically in FIG. 4. The illustrated mass spectrometer 120 includes a housing 122, a continuous ion source 6, and an interface member 10 in the form of a plate having an orifice 14. Downstream (used with reference to the normal direction of ion flow) from ion source 6 is provided a skimmer 130 with skimmer orifice 134, beam formation and guide section 136, the pulser 18, and an analyzer section 160 which includes detector 180. A power supply 200 is capable of providing the required series of potential difference pulses across electrodes R and P0 as a waveform 40a shown in FIG. 5A. One or more pumps (not shown) are provided to maintain required pressures downstream of interface member 10. Components of such a mass spectrometer 120, other than pulser 18, and their operation, are well known and are described, for example, in U.S. Pat. No. 5,689,111 and the references cited herein, which are incorporated herein by reference. It will be appreciated though, that the present invention may be applied to any type of mass spectrometer where packets (or pulses) of ions are to be provided to the analyzer from an ion source that is continuous (or at least is more "continuous" than the required pulses, that is if it produces pulses then those are longer than needed to produce the required packets).
In operation, pulser 18 receives an ion beam from ESI source 6 through orifices 14, 134 and beam formation and guide section 136, and pulser aperture 22. Power supply 200 provides the waveform 40a shown in
During pulse ON time 44a, ions in beam 14 within pulser 18 which do not form ion packet 28 (in particular, ions which are not positioned across grid 24 just before pulse ON 44a is applied) will be deflected onto electrode P0 which is oppositely charged from those ions (as will be appreciated, "oppositely charged" is relative to electrode R such that the ions are attracted to electrode P0 ). That is, the continuous ion beam 14 is deflected toward, and discharged onto electrode P0 before entering aperture 22. Thus, during pulse ON times after packet 28 has been extracted, essentially no stray ions can pass through grid 24 and enter the mass analyzer section 160 (as illustrated by time 60 in FIG. 5B). Only ions indicated at 58a in
It will be seen then, that use of the foregoing method using a pulser waveform 40a (
The foregoing benefit can be better appreciated with reference to a conventional pulser operation. In particular, in a conventional pulser in a TOFMS instrument using an electrospray ion source 10, the time needed for accelerating ions to form ion packet 28 is about 1.4 μ under typical ion optical conditions such as the following:
Predetermined highest mass of interest=1000 amu
Acceleration Voltage (potential difference between R and P0 during pulse ON) =1000 V
Distance between the electrodes R and P0:10 mm
Therefore, in a conventional TOFMS, the pulse ON may only be approximately 2 μs. In a typical TOFMS instrument with 2 meters effective flight path and an ion energy of 5 keV, the analysis time for ion mass of 1000 amu is about 65 microseconds. During the pulse "off" period (63 μs), ions are able to continuously "leak" into the analyzer, resulting a continuous background noise. On the other hand, for a typical electrospray ion source with initial ion energy of 30 eV, the fill time is only 8 μs for a typical ion pulse with an extraction aperture (grid 24 diameter) of 20 mm. In the method of the present invention, the extraction pulse (pulse ON) may for example be 57 μs instead of 2 μs, with pulse OFF (filling time) about 8 or 10 μs. During this substantially longer pulse ON period of the present invention, ions cannot readily enter the mass analyzer. Continuous background ion noise may therefore be substantially reduced.
A particular example of the present invention is illustrated in comparison to a conventional method. In particular, a multi-element analyte solution (2 ppb in concentration) was provided to an inductively couple plasma time-of-flight mass spectrometer (ICP-TOFMS) for a 10 second integrated detection time. The effective flight path of TOFMS and ion energy are 1 meter and 900 eV, respectively. It requires 36.4 μs for ions of highest mass, 238U in the sample, to reach the detector 180. On the other hand, only 1.8 μs is needed for accelerating ions out of the ion pulser 18, which is 10 mm in width (distance between R and P0) using repeller pulse of 150 V. In one case, a conventional pulser as illustrated in
It will be appreciated that in the present invention, some benefit in terms of reduced leakage can be gained over conventional pulser operation where the pulse ON time is substantially greater than required to extract ion packet 28 (for example, at least 2, 4 or even 10 times longer, or with the pulse ON times longer than the pulse OFF times). However, it is preferred that the pulse ON time is the time required for ions of a predetermined highest mass of interest to be analyzed by the analyzer section 160, minus the time required to refill the 20 region of beam 14 from which the ion packet 28 is extracted (that is, the region across grid 24) with ions of the predetermined highest mass. This may be seen, for example, with reference to
Various further modifications to the particular embodiments described above are, of course, possible. Accordingly, the present invention is not limited to the particular embodiments described in detail above.
Myerholtz, Carl A., Yefchak, George, Li, Ganggiang
Patent | Priority | Assignee | Title |
10950425, | Aug 16 2016 | Micromass UK Limited | Mass analyser having extended flight path |
11049712, | Aug 06 2017 | MASS SPECTROMETRY CONSULTING LTD | Fields for multi-reflecting TOF MS |
11081332, | Aug 06 2017 | Micromass UK Limited | Ion guide within pulsed converters |
11205568, | Aug 06 2017 | MASS SPECTROMETRY CONSULTING LTD ; Micromass UK Limited | Ion injection into multi-pass mass spectrometers |
11211238, | Aug 06 2017 | Micromass UK Limited | Multi-pass mass spectrometer |
11239067, | Aug 06 2017 | MASS SPECTROMETRY CONSULTING LTD | Ion mirror for multi-reflecting mass spectrometers |
11295944, | Aug 06 2017 | Micromass UK Limited | Printed circuit ion mirror with compensation |
11309175, | May 05 2017 | Micromass UK Limited | Multi-reflecting time-of-flight mass spectrometers |
11328920, | May 26 2017 | Micromass UK Limited | Time of flight mass analyser with spatial focussing |
11342175, | May 10 2018 | Micromass UK Limited | Multi-reflecting time of flight mass analyser |
11367608, | Apr 20 2018 | Micromass UK Limited | Gridless ion mirrors with smooth fields |
11587779, | Jun 28 2018 | MASS SPECTROMETRY CONSULTING LTD ; Micromass UK Limited | Multi-pass mass spectrometer with high duty cycle |
11621156, | May 10 2018 | Micromass UK Limited | Multi-reflecting time of flight mass analyser |
11756782, | Aug 06 2017 | Micromass UK Limited | Ion mirror for multi-reflecting mass spectrometers |
11817303, | Aug 06 2017 | MASS SPECTROMETRY CONSULTING LTD | Accelerator for multi-pass mass spectrometers |
11848185, | Feb 01 2019 | Micromass UK Limited | Electrode assembly for mass spectrometer |
11881387, | May 24 2018 | Micromass UK Limited | TOF MS detection system with improved dynamic range |
6647347, | Jul 26 2000 | Agilent Technologies, Inc. | Phase-shifted data acquisition system and method |
6870157, | May 23 2002 | The Board of Trustees of the Leland Stanford Junior | Time-of-flight mass spectrometer system |
6998605, | May 25 2000 | Agilent Technologies, Inc.; Agilent Technologies | Apparatus for delivering ions from a grounded electrospray assembly to a vacuum chamber |
7031877, | Jun 08 2001 | University of Maine; Stillwater Scientific Instruments; Spectrum Square Associates, Inc. | Spectroscopy instrument using broadband modulation and statistical estimation techniques to account for component artifacts |
7041966, | May 25 2000 | Agilent Technologies, Inc. | Apparatus for delivering ions from a grounded electrospray assembly to a vacuum chamber |
7259368, | May 25 2000 | Agilent Technologies, Inc. | Apparatus for delivering ions from a grounded electrospray assembly to a vacuum chamber |
7368708, | May 25 2000 | Agilent Technologies, Inc | Apparatus for producing ions from an electrospray assembly |
7403867, | Jun 08 2001 | University of Maine; Stillwater Scientific Instruments; Spectrum Square Associates | Spectroscopy instrument using broadband modulation and statistical estimation techniques to account for component artifacts |
7619213, | Aug 03 2006 | Agilent Technologies, Inc | Ion extraction pulser and method for mass spectrometry |
7755035, | Aug 30 2006 | HITACHI HIGH-TECH CORPORATION | Ion trap time-of-flight mass spectrometer |
8183524, | Dec 14 2006 | Micromass UK Limited | Mass spectrometer having time of flight mass analyser |
Patent | Priority | Assignee | Title |
5689111, | Aug 09 1996 | PerkinElmer Health Sciences, Inc | Ion storage time-of-flight mass spectrometer |
6107625, | May 30 1997 | BRUKER DALTONICS, INC | Coaxial multiple reflection time-of-flight mass spectrometer |
6285027, | Dec 04 1998 | MDS ANALYTICAL TECHNOLOGIES, A BUSINESS UNIT OF MDS INC ; APPLIED BIOSYSTEMS CANADA LIMITED | MS/MS scan methods for a quadrupole/time of flight tandem mass spectrometer |
6300626, | Aug 17 1998 | BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY, THE | Time-of-flight mass spectrometer and ion analysis |
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